Supplemental Results. Analysis of autoimmune disease- and trait-associated SNP sets
Mikhail Dozmorov, Lukas R. Cara, Cory B. Giles, Bridget T. McInnes, Jonathan D. Wren
We analyzed 39 autoimmune disease- and trait-associated SNP sets, obtained from the Supplemental table 1 of the Farh, K. K.-H., Marson, A., Zhu, J., Kleinewietfeld, M., Housley, W. J., Beik, S., … Bernstein, B. E. (2014). “Genetic and epigenetic fine mapping of causal autoimmune disease variants”“ Nature. doi:10.1038/nature13835.
First, we re-created the heatmap of shared genetic features among the autoimmune diseases and traits, that is, counts of genomic elements overlapping between pairs of terms. We will use this heatmap as a reference point to compare with the heatmaps produced by the regulatory similarity analysis.
Analysis of all regulatory datasets
Although we used 4,498 regulatory datasets from the ENCODE project processed with the use with GenomeRunner, some regulatory datasets show not statistically significant enrichments in any of the 39 SNP sets. We removed these datasets as non-informative, and kept the remaining 2,969 regulatory datasets.
## [1] 4498 39## [1] 2969 39We visualized the matrix of pair-wise pearson correlation coefficients among the term-specific regulatory enrichment profiles.
We then compared how regulatory similarity correlates with shared genomic features similarity. pearson correlation coefficient between the two is:
## [1] 0.6680046The top 10 pairs of disease- aassociated SNPs are most similar with each other. The correlation coefficient shows pearson correlation coefficient among the regulatory enrichment profiles for each term-specific SNP set.
##
## --------------------------------------------------------------------------
## Disease 1 Disease 2 Corr. coefficient
## ------------------------- ---------------------------- -------------------
## Multiple_sclerosis Systemic_lupus_erythematosus 0.4557
##
## Celiac_disease Multiple_sclerosis 0.4392
##
## Kawasaki_disease Systemic_lupus_erythematosus 0.4383
##
## Primary_biliary_cirrhosis Systemic_lupus_erythematosus 0.3928
##
## HDL_cholesterol LDL_cholesterol 0.389
##
## Platelet_counts Triglycerides 0.3847
##
## Rheumatoid_arthritis Ulcerative_colitis 0.3566
##
## HDL_cholesterol Triglycerides 0.3503
##
## Multiple_sclerosis Primary_biliary_cirrhosis 0.3322
##
## LDL_cholesterol Triglycerides 0.2817
## --------------------------------------------------------------------------The regulatory similarity dendrogram can be divided into four separate clusters:
## Cluster01 has 5 members
## Platelet_counts
## Triglycerides
## Liver_enzyme_levels_gamma_glutamyl_transferase
## LDL_cholesterol
## HDL_cholesterol
##
## Cluster02 has 14 members
## Bone_mineral_density
## Creatinine_levels
## Chronic_kidney_disease
## Urate_levels
## Vitiligo
## Type_2_diabetes
## Fasting_glucose_related_traits
## Alzheimers_combined
## Restless_legs_syndrome
## Ankylosing_spondylitis
## Primary_sclerosing_cholangitis
## Systemic_sclerosis
## Red_blood_cell_traits
## Migraine
##
## Cluster03 has 5 members
## Multiple_sclerosis
## Celiac_disease
## Primary_biliary_cirrhosis
## Systemic_lupus_erythematosus
## Kawasaki_disease
##
## Cluster04 has 15 members
## Type_1_diabetes
## Behcets_disease
## Juvenile_idiopathic_arthritis
## Renal_function_related_traits_BUN
## Asthma
## Allergy
## Progressive_supranuclear_palsy
## Psoriasis
## Autoimmune_thyroiditis
## Crohns_disease
## Rheumatoid_arthritis
## Ulcerative_colitis
## Alopecia_areata
## C_reactive_protein
## Atopic_dermatitis
## We estimated the differences in regulatory associations of term-secific SNP sets.
The first column shows names of regulatory datasets. The following two columns show the average p-values of the cluster-specific SNP sets-regulatory associations. The smaller a p-value is, the more SNPs in a cluster enriched in corresponsing regulatory dataset. A “-” sign indicates that an association is underrepresented (depleted). The “adj.P.Val” column shows whether a difference in the associations between the clusters is statistically significantly different. The last column shows descriptions of the regulatory datasets. The tables were sorted by “adj.P.Val” column; the top 10 or less most significantly different associations are shown.
## [1] "c1 vs. c2 , number of degs significant at adj.p.val<0.5: 38"
##
## ---------------------------------------------------------------------------------------------------------------
## Row.names c1 c2 adj.P.Val V2
## --------------------------------------------------- --------- ------- ----------- -----------------------------
## wgEncodeSydhTfbsK562Pol2Ifng30StdPk 0.006469 0.9072 0.001309 K562 Pol2 Standard IFNg 30min
## ChIP-seq Peaks from
## ENCODE/SYDH
##
## wgEncodeHaibTfbsHepg2P300V0416101PkRep2 0.00722 0.7239 0.001309 HepG2 p300 v041610.1 ChIP-seq
## Peaks Rep 2 from ENCODE/HAIB
##
## wgEncodeOpenChromChipHepg2Pol2Pk 6.913e-07 -0.6861 0.002655 HepG2 Pol2 TFBS ChIP-seq
## Peaks from
## ENCODE/OpenChrom-UTA
##
## wgEncodeHaibTfbsHepg2Pol24h8V0416102PkRep2 8.983e-07 -0.5865 0.007927 HepG2 Pol2-4H8 v041610.2
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeGisRnaPetNhekNucleusPapClustersRep1 8.839e-05 0.9334 0.008137 NHEK nucleus polyA+
## clone-free RNA PET Clusters
## Rep 1 from ENCODE/GIS
##
## wgEncodeUwHistoneH7esH3k36me3StdDiffa5dHotspotsRep2 0.005028 0.8859 0.008137 H7-hESC H3K36me3 diffProtA 5
## d Histone Mod ChIP-seq
## Hotspots 2 from ENCODE/UW
##
## wgEncodeBroadHistoneNhekH3k79me2Pk 1.5e-05 -0.5031 0.008137 NHEK H3K79me2 Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeHaibTfbsHepg2Mybl2sc81192V0422111PkRep1 0.005722 0.9924 0.008363 HepG2 MYBL2 v042211.1
## ChIP-seq Peaks Rep 1 from
## ENCODE/HAIB
##
## wgEncodeSydhTfbsHepg2Pol2IggrabPk 0.0003379 -0.7955 0.008975 HEPG2 Pol2 IgG-rab ChIP-seq
## Peaks from ENCODE/SYDH
##
## wgEncodeHaibTfbsHepg2Pol2Pcr2xPkRep2 0.001453 -0.8593 0.01037 HepG2 Pol2 PCR2x ChIP-seq
## Peaks Rep 2 from ENCODE/HAIB
## ---------------------------------------------------------------------------------------------------------------
##
## [1] "c1 vs. c3 , number of degs significant at adj.p.val<0.5: 172"
##
## ------------------------------------------------------------------------------------------------------------
## Row.names c1 c3 adj.P.Val V2
## ------------------------------------------------ -------- --------- ----------- ----------------------------
## wgEncodeOpenChromFaireGm19239Pk -0.08204 0.0001051 1.38e-09 GM19239 FAIRE Peaks from
## ENCODE/OpenChrom(UNC)
##
## wgEncodeHaibTfbsGm12878Nficsc81335V0422111PkRep2 -0.1304 0.002245 6.733e-08 GM12878 NFIC v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Nficsc81335V0422111PkRep1 -0.05001 2.709e-06 2.289e-07 GM12878 NFIC v042211.1
## ChIP-seq Peaks Rep 1 from
## ENCODE/HAIB
##
## wgEncodeOpenChromSynthGm18507Pk -0.4051 0.0004778 6.783e-07 GM18507 DNaseI/FAIRE/ChIP
## Synthesis from
## ENCODE/OpenChrom
##
## wgEncodeOpenChromFaireGm18507Pk -0.3038 4.213e-05 8.87e-06 GM18507 FAIRE Peaks from
## ENCODE/OpenChrom(UNC)
##
## wgEncodeUwDnaseGm12865HotspotsRep2 -0.3793 8.456e-06 1.22e-05 GM12865 DNaseI HS HotSpots
## Rep 2 from ENCODE/UW
##
## wgEncodeBroadHistoneGm12878H3k4me2StdPk -0.06231 9.346e-10 1.237e-05 GM12878 H3K4me2 Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneDnd41H3k09acPk -0.6002 2.678e-05 1.298e-05 Dnd41 H3K9ac Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeUwDnaseGm12865HotspotsRep1 -0.2387 8.471e-05 2.134e-05 GM12865 DNaseI HS HotSpots
## Rep 1 from ENCODE/UW
##
## wgEncodeBroadHistoneGm12878H3k9acStdPk -0.05389 5.217e-13 2.851e-05 GM12878 H3K9ac Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
## ------------------------------------------------------------------------------------------------------------
##
## [1] "c1 vs. c4 , number of degs significant at adj.p.val<0.5: 85"
##
## -----------------------------------------------------------------------------------------------------------------
## Row.names c1 c4 adj.P.Val V2
## --------------------------------------------------- ---------- -------- ----------- -----------------------------
## wgEncodeHaibTfbsHepg2P300V0416101PkRep2 0.00722 0.9498 0.0007524 HepG2 p300 v041610.1 ChIP-seq
## Peaks Rep 2 from ENCODE/HAIB
##
## wgEncodeSydhTfbsK562Pol2Ifng30StdPk 0.006469 0.6275 0.001175 K562 Pol2 Standard IFNg 30min
## ChIP-seq Peaks from
## ENCODE/SYDH
##
## wgEncodeUwHistoneH7esH3k36me3StdDiffa5dHotspotsRep2 0.005028 -0.4649 0.001175 H7-hESC H3K36me3 diffProtA 5
## d Histone Mod ChIP-seq
## Hotspots 2 from ENCODE/UW
##
## wgEncodeGisRnaPetHepg2CytosolPapClustersRep1 6.141e-06 -0.01792 0.001175 HepG2 cytosol polyA+
## clone-based RNA PET Clusters
## Rep 1 from ENCODE/GIS
##
## wgEncodeGisRnaPetNhekNucleusPapClustersRep1 8.839e-05 -0.2856 0.001175 NHEK nucleus polyA+
## clone-free RNA PET Clusters
## Rep 1 from ENCODE/GIS
##
## wgEncodeOpenChromChipHepg2Pol2Pk 6.913e-07 -0.6948 0.001175 HepG2 Pol2 TFBS ChIP-seq
## Peaks from
## ENCODE/OpenChrom-UTA
##
## wgEncodeBroadHistoneHuvecH3k79me2Pk 2.13e-05 -0.106 0.001175 HUVEC H3K79me2 Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneNhekH3k79me2Pk 1.5e-05 -0.1112 0.001309 NHEK H3K79me2 Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeGisRnaPetHepg2NucleusPapClustersRep1 6.638e-06 -0.02357 0.002597 HepG2 nucleus polyA+
## clone-based RNA PET Clusters
## Rep 1 from ENCODE/GIS
##
## wgEncodeBroadHistoneHuvecH3k27me3StdPk -4.101e-05 0.1422 0.003049 HUVEC H3K27me3 Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
## -----------------------------------------------------------------------------------------------------------------
##
## [1] "c2 vs. c3 , number of degs significant at adj.p.val<0.5: 159"
##
## -------------------------------------------------------------------------------------------------------------
## Row.names c2 c3 adj.P.Val V2
## ------------------------------------------------ -------- --------- ----------- -----------------------------
## wgEncodeOpenChromFaireGm19239Pk -0.3865 0.0001051 3.218e-10 GM19239 FAIRE Peaks from
## ENCODE/OpenChrom(UNC)
##
## wgEncodeOpenChromSynthGm18507Pk -0.566 0.0004778 2.006e-08 GM18507 DNaseI/FAIRE/ChIP
## Synthesis from
## ENCODE/OpenChrom
##
## wgEncodeHaibTfbsGm12878Nficsc81335V0422111PkRep1 -0.2202 2.709e-06 2.006e-08 GM12878 NFIC v042211.1
## ChIP-seq Peaks Rep 1 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Nficsc81335V0422111PkRep2 -0.517 0.002245 2.708e-08 GM12878 NFIC v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeBroadHistoneGm12878H3k4me2StdPk -0.02211 9.346e-10 8.134e-08 GM12878 H3K4me2 Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeUwDnaseGm12865HotspotsRep2 -0.2974 8.456e-06 1.038e-07 GM12865 DNaseI HS HotSpots
## Rep 2 from ENCODE/UW
##
## wgEncodeBroadHistoneDnd41H3k09acPk -0.4638 2.678e-05 1.161e-07 Dnd41 H3K9ac Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeOpenChromFaireGm18507Pk -0.4293 4.213e-05 1.561e-07 GM18507 FAIRE Peaks from
## ENCODE/OpenChrom(UNC)
##
## wgEncodeBroadHistoneDnd41H3k04me1Pk -0.1887 3.207e-09 2.345e-07 Dnd41 H3K4me1 Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeSydhTfbsGm12878Pol2s2IggmusPk -0.24 5.349e-06 3.092e-07 GM12878 Pol2 S2 IgG-mus
## ChIP-seq Peaks from
## ENCODE/SYDH
## -------------------------------------------------------------------------------------------------------------
##
## [1] "c3 vs. c4 , number of degs significant at adj.p.val<0.5: 152"
##
## ------------------------------------------------------------------------------------------------------------
## Row.names c3 c4 adj.P.Val V2
## ------------------------------------------------ --------- ------- ----------- -----------------------------
## wgEncodeOpenChromFaireGm19239Pk 0.0001051 0.6658 1.398e-08 GM19239 FAIRE Peaks from
## ENCODE/OpenChrom(UNC)
##
## wgEncodeOpenChromSynthGm18507Pk 0.0004778 0.6495 6.122e-07 GM18507 DNaseI/FAIRE/ChIP
## Synthesis from
## ENCODE/OpenChrom
##
## wgEncodeBroadHistoneDnd41H3k09acPk 2.678e-05 -0.8745 8.889e-07 Dnd41 H3K9ac Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneDnd41H3k04me1Pk 3.207e-09 -0.7861 2.207e-06 Dnd41 H3K4me1 Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeHaibTfbsGm12878Nficsc81335V0422111PkRep1 2.709e-06 0.2551 2.391e-06 GM12878 NFIC v042211.1
## ChIP-seq Peaks Rep 1 from
## ENCODE/HAIB
##
## wgEncodeOpenChromFaireGm18507Pk 4.213e-05 0.6812 2.798e-06 GM18507 FAIRE Peaks from
## ENCODE/OpenChrom(UNC)
##
## wgEncodeUwDnaseGm12865HotspotsRep2 8.456e-06 0.5282 2.825e-06 GM12865 DNaseI HS HotSpots
## Rep 2 from ENCODE/UW
##
## wgEncodeHaibTfbsGm12878Nficsc81335V0422111PkRep2 0.002245 0.4559 3.584e-06 GM12878 NFIC v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeBroadHistoneGm12878H3k4me2StdPk 9.346e-10 0.3976 5.523e-06 GM12878 H3K4me2 Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeSydhTfbsGm12878Chd1a301218aIggmusPk 1.229e-06 0.7272 7.359e-06 GM12878 CHD1 IgG-mus ChIP-seq
## Peaks from ENCODE/SYDH
## ------------------------------------------------------------------------------------------------------------## [1] "Counts of regulatory elements differentially associated with each group"##
## ----------------------------
## c1 c2 c3 c4
## -------- ---- ---- ---- ----
## **c1** 0 38 172 85
##
## **c2** 0 0 159 0
##
## **c3** 0 0 0 152
##
## **c4** 0 0 0 0
## ----------------------------Summary
The differences in regulatory associations are attributed to the clusters 1 and 3.
The cluster 1 (Platelet_counts, Triglycerides, Liver_enzyme_levels_gamma_glutamyl_transferase, LDL_cholesterol, HDL_cholesterol) showed enrichment in PolII, H3K36me3 and H3K79me2 histone modification marks. The signals was derived predominantly from cancer-related cell lines, such as HepG2 (liver hepatocellular carcinoma), K562 (myelogeneous leukemia), A549 (adenocarcinomic human alveolar basal epithelial cells).
The cluster 3 (Multiple_sclerosis, Celiac_disease, Primary_biliary_cirrhosis, Systemic_lupus_erythematosus, Kawasaki_disease) showed strong enrichment in B-cell derived signal. The most predominant cell type was Gm12878 (B lymphoblastoid cell line), CD20+ B cells, although some signal came from Dnd41 cells (T-ALL), T helper cells 1 and 2, and CD14+ monocytes. DNAse hypersensitive sites were predominant type of signal enriched in the disease-associated SNPs from this cluster, followed by H3K4 mono-/di- and trimethylation, PolII, H3K79me2, H3K27 trimethylation and acetylation, and the CTCF, NFkB, NFATC1, STAT5A and other transcription factor binding sites
Co-morbidity similarity analysis
We used the data from Hidalgo CA, Blumm N, Barabasi A-L, Christakis NA. PLoS Computational Biology, 5(4):e1000353 doi:10.1371/journal.pcbi.1000353, available at http://barabasilab.neu.edu/projects/hudine/resource/data/data.html. These data provide co-morbidity measurements among pairs of diseases. We map autoimmune disease- and trait names to 3-digits ICD9 codes and evaluate how co-morbidity measurements correlate with regulatory similarity measurements. We used Phi measurement of co-morbidity. The pearson correlation coefficient of Phi and regulatory similarity is:
## [1] 0.4011363Iridescent literature similarity
## [1] "sharedRels correlation with regulatory similarity"
## [1] 0.3657238
## [1] "obsExp correlation with regulatory similarity"
## [1] 0.5619774
## [1] "minMim correlation with regulatory similarity"
## [1] 0.7311888
## [1] "directStr correlation with regulatory similarity"
## [1] 0.1968273
## [1] "relOverlap correlation with regulatory similarity"
## [1] 0.3851007
## [1] "misn correlation with regulatory similarity"
## [1] 0.7310631UMLS literature similarity
## [1] "msh.path correlation with regulatory similarity"
## [1] 0.3092355
## [1] "snomedct.path correlation with regulatory similarity"
## [1] 0.8287126Analysis of TFBSs
We also performed regulatory similarity analysis using subsets of regulatory datasets, such as Transcription Factor Binding Sites or Histone Modification Marks. Here, out of all regulatory datasets, we selected only TFBSs.
## [1] 1954 39## [1] 1259 39We visualized the matrix of pair-wise pearson correlation coefficients among the term-specific regulatory enrichment profiles.
We then compared how regulatory similarity correlates with shared genomic features similarity. pearson correlation coefficient between the two is:
## [1] 0.6298022The top 10 pairs of disease-associated SNPs are most similar with each other.
##
## -----------------------------------------------------------------------
## Disease 1 Disease 2 Corr. coefficient
## ---------------------- ---------------------------- -------------------
## Kawasaki_disease Systemic_lupus_erythematosus 0.7189
##
## HDL_cholesterol LDL_cholesterol 0.6883
##
## Multiple_sclerosis Systemic_lupus_erythematosus 0.6683
##
## Ankylosing_spondylitis Crohns_disease 0.6548
##
## Bone_mineral_density Type_2_diabetes 0.584
##
## HDL_cholesterol Triglycerides 0.5278
##
## Ankylosing_spondylitis Ulcerative_colitis 0.5021
##
## Kawasaki_disease Rheumatoid_arthritis 0.4912
##
## Alzheimers_combined Type_2_diabetes 0.4884
##
## Kawasaki_disease Multiple_sclerosis 0.4872
## -----------------------------------------------------------------------The regulatory similarity dendrogram can be divided into four separate clusters:
## Cluster01 has 6 members
## Multiple_sclerosis
## Systemic_lupus_erythematosus
## Kawasaki_disease
## Psoriasis
## Celiac_disease
## Ulcerative_colitis
##
## Cluster02 has 6 members
## Allergy
## Rheumatoid_arthritis
## Autoimmune_thyroiditis
## Primary_biliary_cirrhosis
## Migraine
## Systemic_sclerosis
##
## Cluster03 has 4 members
## Chronic_kidney_disease
## Type_2_diabetes
## Bone_mineral_density
## Alzheimers_combined
##
## Cluster04 has 5 members
## Urate_levels
## Liver_enzyme_levels_gamma_glutamyl_transferase
## Triglycerides
## HDL_cholesterol
## LDL_cholesterol
##
## Cluster05 has 2 members
## Crohns_disease
## Ankylosing_spondylitis
##
## Cluster06 has 16 members
## Renal_function_related_traits_BUN
## Fasting_glucose_related_traits
## Platelet_counts
## Juvenile_idiopathic_arthritis
## Atopic_dermatitis
## Red_blood_cell_traits
## C_reactive_protein
## Primary_sclerosing_cholangitis
## Alopecia_areata
## Asthma
## Behcets_disease
## Progressive_supranuclear_palsy
## Creatinine_levels
## Restless_legs_syndrome
## Type_1_diabetes
## Vitiligo
## We estimated the differences in regulatory associations of term-secific SNP sets.
The first column shows names of regulatory datasets. The following two columns show the average p-values of the cluster-specific SNP sets-regulatory associations. The smaller a p-value is, the more SNPs in a cluster enriched in corresponsing regulatory dataset. A “-” sign indicates that an association is underrepresented (depleted). The “adj.P.Val” column shows whether a difference in the associations between the clusters is statistically significantly different. The last column shows descriptions of the regulatory datasets. The tables were sorted by “adj.P.Val” column; the top 10 or less most significantly different associations are shown.
## [1] "c1 vs. c2 , number of degs significant at adj.p.val<0.5: 62"
##
## -------------------------------------------------------------------------------------------------------------
## Row.names c1 c2 adj.P.Val V2
## -------------------------------------------------- --------- ------ ----------- -----------------------------
## wgEncodeHaibTfbsGm12878Runx3sc101553V0422111PkRep2 8.939e-05 0.561 3.281e-09 GM12878 RUNX3 v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Pmlsc71910V0422111PkRep2 1.027e-05 0.507 3.952e-09 GM12878 PML v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Stat5asc74442V0422111PkRep2 5.806e-05 0.8614 5.249e-09 GM12878 STAT5A v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Pou2f2Pcr1xPkRep2 0.003845 0.9554 1.375e-07 GM12878 POU2F2 PCR1x ChIP-seq
## Peaks Rep 2 from ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12891Pol2Pcr1xPkRep1 0.004814 0.6935 2.882e-07 GM12891 Pol2 PCR1x ChIP-seq
## Peaks Rep 1 from ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Stat5asc74442V0422111PkRep1 0.000687 0.906 2.89e-07 GM12878 STAT5A v042211.1
## ChIP-seq Peaks Rep 1 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Bclaf101388V0416101PkRep2 0.001796 0.4804 5.46e-07 GM12878 BCLAF1 v041610.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Pol2Pcr2xPkRep1 0.0001325 0.6133 5.46e-07 GM12878 Pol2 PCR2x ChIP-seq
## Peaks Rep 1 from ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Mta3sc81325V0422111PkRep2 7.449e-07 0.4086 5.46e-07 GM12878 MTA3 v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Atf2sc81188V0422111PkRep1 0.0001343 0.5215 4.325e-06 GM12878 ATF2 v042211.1
## ChIP-seq Peaks Rep 1 from
## ENCODE/HAIB
## -------------------------------------------------------------------------------------------------------------
##
## [1] "c1 vs. c3 , number of degs significant at adj.p.val<0.5: 65"
##
## -----------------------------------------------------------------------------------------------------------------
## Row.names c1 c3 adj.P.Val V2
## -------------------------------------------------- --------- ---------- ----------- -----------------------------
## wgEncodeHaibTfbsGm12878Pmlsc71910V0422111PkRep2 1.027e-05 -0.01199 3.087e-12 GM12878 PML v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Runx3sc101553V0422111PkRep2 8.939e-05 -0.07637 1.033e-11 GM12878 RUNX3 v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Stat5asc74442V0422111PkRep2 5.806e-05 -0.02658 1.402e-11 GM12878 STAT5A v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Pol2Pcr2xPkRep1 0.0001325 -0.01003 1.366e-10 GM12878 Pol2 PCR2x ChIP-seq
## Peaks Rep 1 from ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Mta3sc81325V0422111PkRep2 7.449e-07 -0.0008688 1.366e-10 GM12878 MTA3 v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Pou2f2Pcr1xPkRep2 0.003845 -0.09044 1.484e-10 GM12878 POU2F2 PCR1x ChIP-seq
## Peaks Rep 2 from ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12891Pol2Pcr1xPkRep1 0.004814 -0.2148 1.16e-09 GM12891 Pol2 PCR1x ChIP-seq
## Peaks Rep 1 from ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Bclaf101388V0416101PkRep2 0.001796 -0.1952 1.91e-09 GM12878 BCLAF1 v041610.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Atf2sc81188V0422111PkRep2 0.0007129 -0.05776 1.951e-09 GM12878 ATF2 v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Runx3sc101553V0422111PkRep1 0.0001092 -0.01052 4.089e-09 GM12878 RUNX3 v042211.1
## ChIP-seq Peaks Rep 1 from
## ENCODE/HAIB
## -----------------------------------------------------------------------------------------------------------------
##
## [1] "c1 vs. c4 , number of degs significant at adj.p.val<0.5: 77"
##
## ---------------------------------------------------------------------------------------------------------------
## Row.names c1 c4 adj.P.Val V2
## -------------------------------------------------- --------- -------- ----------- -----------------------------
## wgEncodeHaibTfbsGm12878Runx3sc101553V0422111PkRep2 8.939e-05 -0.1192 1.486e-11 GM12878 RUNX3 v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Pmlsc71910V0422111PkRep2 1.027e-05 -0.1599 5.185e-11 GM12878 PML v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Stat5asc74442V0422111PkRep2 5.806e-05 -0.2564 3.98e-10 GM12878 STAT5A v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Nficsc81335V0422111PkRep1 8.776e-06 -0.0344 1.617e-08 GM12878 NFIC v042211.1
## ChIP-seq Peaks Rep 1 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Foxm1sc502V0422111PkRep1 0.0002931 -0.09224 1.617e-08 GM12878 FOXM1 v042211.1
## ChIP-seq Peaks Rep 1 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Stat5asc74442V0422111PkRep1 0.000687 -0.3028 1.617e-08 GM12878 STAT5A v042211.1
## ChIP-seq Peaks Rep 1 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Bclaf101388V0416101PkRep2 0.001796 -0.5678 1.617e-08 GM12878 BCLAF1 v041610.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Atf2sc81188V0422111PkRep2 0.0007129 -0.2449 1.898e-08 GM12878 ATF2 v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12891Pol2Pcr1xPkRep1 0.004814 -0.6803 1.898e-08 GM12891 Pol2 PCR1x ChIP-seq
## Peaks Rep 1 from ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Pou2f2Pcr1xPkRep2 0.003845 -0.6217 2.253e-08 GM12878 POU2F2 PCR1x ChIP-seq
## Peaks Rep 2 from ENCODE/HAIB
## ---------------------------------------------------------------------------------------------------------------
##
## [1] "c1 vs. c6 , number of degs significant at adj.p.val<0.5: 66"
##
## --------------------------------------------------------------------------------------------------------------
## Row.names c1 c6 adj.P.Val V2
## -------------------------------------------------- --------- ------- ----------- -----------------------------
## wgEncodeHaibTfbsGm12878Runx3sc101553V0422111PkRep2 8.939e-05 -0.9353 2.59e-12 GM12878 RUNX3 v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Pmlsc71910V0422111PkRep2 1.027e-05 -0.9168 3.592e-12 GM12878 PML v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Stat5asc74442V0422111PkRep2 5.806e-05 0.7588 5.061e-11 GM12878 STAT5A v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Bclaf101388V0416101PkRep2 0.001796 -0.9275 4.125e-10 GM12878 BCLAF1 v041610.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12891Pol2Pcr1xPkRep1 0.004814 0.9679 5.483e-10 GM12891 Pol2 PCR1x ChIP-seq
## Peaks Rep 1 from ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Pou2f2Pcr1xPkRep2 0.003845 0.9739 8.288e-10 GM12878 POU2F2 PCR1x ChIP-seq
## Peaks Rep 2 from ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Mta3sc81325V0422111PkRep2 7.449e-07 -0.6721 8.288e-10 GM12878 MTA3 v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Stat5asc74442V0422111PkRep1 0.000687 -0.8088 8.414e-10 GM12878 STAT5A v042211.1
## ChIP-seq Peaks Rep 1 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Atf2sc81188V0422111PkRep2 0.0007129 -0.8895 2.672e-09 GM12878 ATF2 v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Pol2Pcr2xPkRep1 0.0001325 0.7987 2.672e-09 GM12878 Pol2 PCR2x ChIP-seq
## Peaks Rep 1 from ENCODE/HAIB
## --------------------------------------------------------------------------------------------------------------
##
## [1] "c2 vs. c3 , number of degs significant at adj.p.val<0.5: 3"
##
## ----------------------------------------------------------------------------------------------------------
## Row.names c2 c3 adj.P.Val V2
## ------------------------------------------------ ------- ---------- ----------- --------------------------
## wgEncodeHaibTfbsGm12878Pol24h8Pcr1xPkRep2 0.01412 -0.0009115 0.03041 GM12878 Pol2-4H8 PCR1x
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12878Mta3sc81325V0422111PkRep2 0.4086 -0.0008688 0.03113 GM12878 MTA3 v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsGm12892Pol24h8V0416102PkRep1 0.1585 -0.004603 0.07884 GM12892 Pol2-4H8 v041610.2
## ChIP-seq Peaks Rep 1 from
## ENCODE/HAIB
## ----------------------------------------------------------------------------------------------------------
##
## [1] "c2 vs. c4 , number of degs significant at adj.p.val<0.5: 11"
##
## ------------------------------------------------------------------------------------------------------------
## Row.names c2 c4 adj.P.Val V2
## ------------------------------------------------ ------- --------- ----------- -----------------------------
## wgEncodeHaibTfbsHepg2Mybl2sc81192V0422111PkRep2 -0.7955 0.0007234 0.0006506 HepG2 MYBL2 v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsHepg2Tead4sc101184V0422111PkRep1 -0.9887 0.001973 0.001469 HepG2 TEAD4 v042211.1
## ChIP-seq Peaks Rep 1 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsHepg2Mybl2sc81192V0422111PkRep1 -0.9952 0.003229 0.002817 HepG2 MYBL2 v042211.1
## ChIP-seq Peaks Rep 1 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsHepg2Foxa1sc6553V0416101PkRep1 -0.8416 0.006962 0.00499 HepG2 FOXA1 6553 v041610.1
## ChIP-seq Peaks Rep 1 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsHepg2Pol24h8V0416102PkRep1 -0.7936 0.0004534 0.01077 HepG2 Pol2-4H8 v041610.2
## ChIP-seq Peaks Rep 1 from
## ENCODE/HAIB
##
## wgEncodeSydhTfbsHepg2Pol2IggrabPk -0.658 0.000279 0.01197 HEPG2 Pol2 IgG-rab ChIP-seq
## Peaks from ENCODE/SYDH
##
## wgEncodeHaibTfbsHepg2Pol24h8V0416102PkRep2 -0.5454 1.017e-06 0.01295 HepG2 Pol2-4H8 v041610.2
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsHepg2Pol2Pcr2xPkRep2 0.9687 0.001153 0.01859 HepG2 Pol2 PCR2x ChIP-seq
## Peaks Rep 2 from ENCODE/HAIB
##
## wgEncodeHaibTfbsHepg2Mbd4sc271530V0422111PkRep1 -0.8289 0.009568 0.02326 HepG2 MBD4 v042211.1 ChIP-seq
## Peaks Rep 1 from ENCODE/HAIB
##
## wgEncodeHaibTfbsHepg2Hey1V0416101PkRep1 -0.9811 0.000285 0.007157
## ------------------------------------------------------------------------------------------------------------
##
## [1] "c3 vs. c4 , number of degs significant at adj.p.val<0.5: 11"
##
## ------------------------------------------------------------------------------------------------------------
## Row.names c3 c4 adj.P.Val V2
## ------------------------------------------------ ------- --------- ----------- -----------------------------
## wgEncodeHaibTfbsHepg2Mybl2sc81192V0422111PkRep2 0.4549 0.0007234 0.007673 HepG2 MYBL2 v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsHepg2Mybl2sc81192V0422111PkRep1 -0.86 0.003229 0.009629 HepG2 MYBL2 v042211.1
## ChIP-seq Peaks Rep 1 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsHepg2Foxa1sc6553V0416101PkRep1 -0.9877 0.006962 0.0199 HepG2 FOXA1 6553 v041610.1
## ChIP-seq Peaks Rep 1 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsHepg2Pol24h8V0416102PkRep2 -0.1786 1.017e-06 0.02195 HepG2 Pol2-4H8 v041610.2
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsHepg2Tead4sc101184V0422111PkRep1 0.3458 0.001973 0.02195 HepG2 TEAD4 v042211.1
## ChIP-seq Peaks Rep 1 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsHepg2Pol2Pcr2xPkRep2 -0.5218 0.001153 0.02202 HepG2 Pol2 PCR2x ChIP-seq
## Peaks Rep 2 from ENCODE/HAIB
##
## wgEncodeSydhTfbsHepg2Pol2IggrabPk -0.4535 0.000279 0.02202 HEPG2 Pol2 IgG-rab ChIP-seq
## Peaks from ENCODE/SYDH
##
## wgEncodeHaibTfbsHepg2Pol24h8V0416102PkRep1 -0.6623 0.0004534 0.02298 HepG2 Pol2-4H8 v041610.2
## ChIP-seq Peaks Rep 1 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsHepg2Mbd4sc271530V0422111PkRep1 -0.986 0.009568 0.07367 HepG2 MBD4 v042211.1 ChIP-seq
## Peaks Rep 1 from ENCODE/HAIB
##
## wgEncodeHaibTfbsHepg2Hey1V0416101PkRep2 -0.6034 0.003643 0.007673
## ------------------------------------------------------------------------------------------------------------
##
## [1] "c3 vs. c6 , number of degs significant at adj.p.val<0.5: 1"
##
## ---------------------------------------------------------------------------------------------------------
## Row.names c3 c6 adj.P.Val V2
## ------------------------------------------------ ---------- ------- ----------- -------------------------
## wgEncodeHaibTfbsGm12878Mta3sc81325V0422111PkRep2 -0.0008688 -0.6721 0.04644 GM12878 MTA3 v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
## ---------------------------------------------------------------------------------------------------------
##
## [1] "c4 vs. c6 , number of degs significant at adj.p.val<0.5: 11"
##
## -----------------------------------------------------------------------------------------------------------
## Row.names c4 c6 adj.P.Val V2
## ------------------------------------------------ --------- ------ ----------- -----------------------------
## wgEncodeHaibTfbsHepg2Mybl2sc81192V0422111PkRep2 0.0007234 0.9488 5.268e-05 HepG2 MYBL2 v042211.1
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsHepg2Tead4sc101184V0422111PkRep1 0.001973 0.9985 0.0001274 HepG2 TEAD4 v042211.1
## ChIP-seq Peaks Rep 1 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsHepg2Mybl2sc81192V0422111PkRep1 0.003229 0.9916 0.0002865 HepG2 MYBL2 v042211.1
## ChIP-seq Peaks Rep 1 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsHepg2Foxa1sc6553V0416101PkRep1 0.006962 0.8901 0.001191 HepG2 FOXA1 6553 v041610.1
## ChIP-seq Peaks Rep 1 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsHepg2Pol24h8V0416102PkRep1 0.0004534 0.6691 0.003514 HepG2 Pol2-4H8 v041610.2
## ChIP-seq Peaks Rep 1 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsHepg2Pol2Pcr2xPkRep2 0.001153 0.6707 0.005071 HepG2 Pol2 PCR2x ChIP-seq
## Peaks Rep 2 from ENCODE/HAIB
##
## wgEncodeHaibTfbsHepg2Pol24h8V0416102PkRep2 1.017e-06 0.4296 0.005513 HepG2 Pol2-4H8 v041610.2
## ChIP-seq Peaks Rep 2 from
## ENCODE/HAIB
##
## wgEncodeHaibTfbsHepg2Mbd4sc271530V0422111PkRep1 0.009568 0.9875 0.005573 HepG2 MBD4 v042211.1 ChIP-seq
## Peaks Rep 1 from ENCODE/HAIB
##
## wgEncodeSydhTfbsHepg2Pol2IggrabPk 0.000279 0.5467 0.005573 HEPG2 Pol2 IgG-rab ChIP-seq
## Peaks from ENCODE/SYDH
##
## wgEncodeHaibTfbsHepg2Hey1V0416101PkRep1 0.000285 0.7581 0.001305
## -----------------------------------------------------------------------------------------------------------## [1] "Counts of regulatory elements differentially associated with each group"##
## --------------------------------------
## c1 c2 c3 c4 c5 c6
## -------- ---- ---- ---- ---- ---- ----
## **c1** 0 62 65 77 0 66
##
## **c2** 0 0 3 11 0 0
##
## **c3** 0 0 0 11 0 1
##
## **c4** 0 0 0 0 0 11
##
## **c5** 0 0 0 0 0 0
##
## **c6** 0 0 0 0 0 0
## --------------------------------------Summary
Now, the same set of diseases is different from the others.
Co-morbidity similarity analysis
We used the data from Hidalgo CA, Blumm N, Barabasi A-L, Christakis NA. PLoS Computational Biology, 5(4):e1000353 doi:10.1371/journal.pcbi.1000353, available at http://barabasilab.neu.edu/projects/hudine/resource/data/data.html. These data provide co-morbidity measurements among pairs of diseases. We map autoimmune disease- and trait names to 3-digits ICD9 codes and evaluate how co-morbidity measurements correlate with regulatory similarity measurements. We used Phi measurement of co-morbidity. The pearson correlation coefficient of Phi and regulatory similarity is:
## [1] 0.3759245Iridescent literature similarity
## [1] "sharedRels correlation with regulatory similarity"
## [1] 0.3484246
## [1] "obsExp correlation with regulatory similarity"
## [1] 0.5045555
## [1] "minMim correlation with regulatory similarity"
## [1] 0.6470513
## [1] "directStr correlation with regulatory similarity"
## [1] 0.2835723
## [1] "relOverlap correlation with regulatory similarity"
## [1] 0.3602434
## [1] "misn correlation with regulatory similarity"
## [1] 0.672326UMLS literature similarity
## [1] "msh.path correlation with regulatory similarity"
## [1] 0.2614632
## [1] "snomedct.path correlation with regulatory similarity"
## [1] 0.7064502Analysis of histone marks
We also performed regulatory similarity analysis using subsets of regulatory datasets, such as Transcription Factor Binding Sites or Histone Modification Marks. Here, out of all regulatory datasets, we selected only Histone marks.
## [1] 721 39## [1] 610 39We visualized the matrix of pair-wise pearson correlation coefficients among the term-specific regulatory enrichment profiles.
We then compared how regulatory similarity correlates with shared genomic features similarity. pearson correlation coefficient between the two is:
## [1] 0.6299304The top 10 pairs of disease-associated SNPs are most similar with each other.
##
## --------------------------------------------------------------------------
## Disease 1 Disease 2 Corr. coefficient
## ------------------------- ---------------------------- -------------------
## Multiple_sclerosis Systemic_lupus_erythematosus 0.6312
##
## Primary_biliary_cirrhosis Systemic_lupus_erythematosus 0.5528
##
## Rheumatoid_arthritis Ulcerative_colitis 0.5467
##
## Multiple_sclerosis Primary_biliary_cirrhosis 0.4959
##
## HDL_cholesterol LDL_cholesterol 0.4798
##
## Kawasaki_disease Systemic_lupus_erythematosus 0.4668
##
## Alzheimers_combined Restless_legs_syndrome 0.4515
##
## HDL_cholesterol Triglycerides 0.4354
##
## Psoriasis Systemic_lupus_erythematosus 0.407
##
## Celiac_disease Multiple_sclerosis 0.4017
## --------------------------------------------------------------------------The regulatory similarity dendrogram can be divided into four separate clusters:
## Cluster01 has 7 members
## Triglycerides
## Platelet_counts
## Liver_enzyme_levels_gamma_glutamyl_transferase
## HDL_cholesterol
## LDL_cholesterol
## Type_2_diabetes
## Fasting_glucose_related_traits
##
## Cluster02 has 6 members
## Celiac_disease
## Multiple_sclerosis
## Primary_biliary_cirrhosis
## Systemic_lupus_erythematosus
## Psoriasis
## Kawasaki_disease
##
## Cluster03 has 10 members
## Crohns_disease
## Autoimmune_thyroiditis
## Allergy
## Vitiligo
## Progressive_supranuclear_palsy
## Red_blood_cell_traits
## Ankylosing_spondylitis
## Primary_sclerosing_cholangitis
## Systemic_sclerosis
## Migraine
##
## Cluster04 has 8 members
## Alzheimers_combined
## Restless_legs_syndrome
## Atopic_dermatitis
## Bone_mineral_density
## Creatinine_levels
## Chronic_kidney_disease
## Urate_levels
## Renal_function_related_traits_BUN
##
## Cluster05 has 8 members
## Type_1_diabetes
## Juvenile_idiopathic_arthritis
## Behcets_disease
## Ulcerative_colitis
## Rheumatoid_arthritis
## Alopecia_areata
## C_reactive_protein
## Asthma
## We estimated the differences in regulatory associations of term-secific SNP sets.
The first column shows names of regulatory datasets. The following two columns show the average p-values of the cluster-specific SNP sets-regulatory associations. The smaller a p-value is, the more SNPs in a cluster enriched in corresponsing regulatory dataset. A “-” sign indicates that an association is underrepresented (depleted). The “adj.P.Val” column shows whether a difference in the associations between the clusters is statistically significantly different. The last column shows descriptions of the regulatory datasets. The tables were sorted by “adj.P.Val” column; the top 10 or less most significantly different associations are shown.
## [1] "c1 vs. c2 , number of degs significant at adj.p.val<0.5: 57"
##
## --------------------------------------------------------------------------------------------------------------
## Row.names c1 c2 adj.P.Val V2
## ----------------------------------------------- ---------- --------- ----------- -----------------------------
## wgEncodeUwHistoneGm12875H3k04me3StdHotspotsRep1 -0.4394 0.0005212 9.005e-07 GM12875 H3K4me3 Histone Mod
## ChIP-seq Hotspots 1 from
## ENCODE/UW
##
## wgEncodeBroadHistoneGm12878H3k9acStdPk -0.01808 3.849e-12 1.828e-06 GM12878 H3K9ac Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneGm12878H3k4me2StdPk -0.008004 8.782e-09 1.828e-06 GM12878 H3K4me2 Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeUwHistoneGm12865H3k04me3StdHotspotsRep2 -0.123 5.452e-07 8.189e-06 GM12865 H3K4me3 Histone Mod
## ChIP-seq Hotspots 2 from
## ENCODE/UW
##
## wgEncodeBroadHistoneGm12878H3k9me3StdPk -2.843e-07 2.129e-10 8.189e-06 GM12878 H3K9me3 Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeUwHistoneGm12865H3k04me3StdHotspotsRep1 -0.1632 2.881e-06 3.078e-05 GM12865 H3K4me3 Histone Mod
## ChIP-seq Hotspots 1 from
## ENCODE/UW
##
## wgEncodeBroadHistoneCd20H3k04me2Pk -0.002374 6.1e-09 3.078e-05 CD20+ H3K4me2 Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneGm12878H3k04me3StdPkV2 -0.02222 4.708e-08 3.425e-05 GM12878 H3K4me3 Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneGm12878H3k04me1StdPkV2 -5.857e-05 6.263e-15 3.615e-05 GM12878 H3K4me1 Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeUwHistoneGm12864H3k04me3StdHotspotsRep2 -0.523 0.003202 3.615e-05 GM12864 H3K4me3 Histone Mod
## ChIP-seq Hotspots 2 from
## ENCODE/UW
## --------------------------------------------------------------------------------------------------------------
##
## [1] "c1 vs. c3 , number of degs significant at adj.p.val<0.5: 6"
##
## -------------------------------------------------------------------------------------------------------
## Row.names c1 c3 adj.P.Val V2
## ------------------------------------------ ---------- ------- ----------- -----------------------------
## wgEncodeBroadHistoneA549H3k79me2Dex100nmPk 0.0001024 -0.9021 0.02348 A549 DEX 100 nM H3K79me2
## Histone Mods by ChIP-seq
## Peaks from ENCODE/Broad
##
## wgEncodeBroadHistoneA549H3k79me2Etoh02Pk 0.0002004 0.8357 0.08259 A549 EtOH 0.02% H3K79me2
## Histone Mods by ChIP-seq
## Peaks from ENCODE/Broad
##
## wgEncodeBroadHistoneNhlfH3k79me2Pk 4.751e-05 0.6981 0.08259 NHLF H3K79me2 Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneHuvecH3k79me2Pk 0.0001697 0.7884 0.08259 HUVEC H3K79me2 Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneNhekH3k79me2Pk 0.0001432 0.7962 0.08259 NHEK H3K79me2 Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneHuvecH3k27me3StdPk -0.0002469 -0.8449 0.08259 HUVEC H3K27me3 Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
## -------------------------------------------------------------------------------------------------------
##
## [1] "c1 vs. c4 , number of degs significant at adj.p.val<0.5: 34"
##
## ---------------------------------------------------------------------------------------------------------
## Row.names c1 c4 adj.P.Val V2
## ------------------------------------------ --------- ---------- ----------- -----------------------------
## wgEncodeBroadHistoneA549H3k79me2Dex100nmPk 0.0001024 -0.1158 0.002307 A549 DEX 100 nM H3K79me2
## Histone Mods by ChIP-seq
## Peaks from ENCODE/Broad
##
## wgEncodeBroadHistoneOsteoH4k20me1Pk 0.007273 -0.09496 0.00362 Osteoblasts H4K20me1 Histone
## Mods by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneNhaH4k20me1Pk 0.002923 -0.1011 0.004216 NH-A H4K20me1 Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneNhekH3k79me2Pk 0.0001432 -0.07455 0.006329 NHEK H3K79me2 Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneA549H3k79me2Etoh02Pk 0.0002004 -0.2685 0.009682 A549 EtOH 0.02% H3K79me2
## Histone Mods by ChIP-seq
## Peaks from ENCODE/Broad
##
## wgEncodeBroadHistoneNhdfadH3k36me3StdPk 0.04191 -0.005215 0.0131 NHDF-Ad H3K36me3 Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneHuvecH3k79me2Pk 0.0001697 -0.3014 0.0131 HUVEC H3K79me2 Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneNhekH3k36me3StdPk 0.002936 -0.02459 0.01416 NHEK H3K36me3 Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneHmecH3k36me3StdPk 0.001914 -0.0002847 0.01711 HMEC H3K36me3 Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneNhlfH3k79me2Pk 4.751e-05 -0.6816 0.02063 NHLF H3K79me2 Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
## ---------------------------------------------------------------------------------------------------------
##
## [1] "c1 vs. c5 , number of degs significant at adj.p.val<0.5: 57"
##
## ---------------------------------------------------------------------------------------------------------
## Row.names c1 c5 adj.P.Val V2
## ------------------------------------------ ---------- --------- ----------- -----------------------------
## wgEncodeBroadHistoneA549H3k79me2Dex100nmPk 0.0001024 -0.007415 4.128e-05 A549 DEX 100 nM H3K79me2
## Histone Mods by ChIP-seq
## Peaks from ENCODE/Broad
##
## wgEncodeBroadHistoneA549H3k79me2Etoh02Pk 0.0002004 -0.0104 0.0003534 A549 EtOH 0.02% H3K79me2
## Histone Mods by ChIP-seq
## Peaks from ENCODE/Broad
##
## wgEncodeBroadHistoneNhaH3k79me2Pk 0.0009854 -0.002468 0.0004093 NH-A H3K79me2 Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneHuvecH3k79me2Pk 0.0001697 -0.0123 0.0004093 HUVEC H3K79me2 Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneOsteoH3k79me2Pk 0.002415 -0.004605 0.0004484 Osteoblasts H3K79me2 Histone
## Mods by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneNhlfH3k79me2Pk 4.751e-05 -0.01706 0.0006228 NHLF H3K79me2 Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneHuvecH3k27me3StdPk -0.0002469 0.01744 0.0006936 HUVEC H3K27me3 Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneHsmmH3k79me2StdPk 0.0006338 -0.0148 0.0006936 HSMM H3K79me2 Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneNhekH3k79me2Pk 0.0001432 -0.02136 0.0006936 NHEK H3K79me2 Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneHsmmH3k27me3StdPk -0.001048 1.409e-09 0.0008928 HSMM H3K27me3 Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
## ---------------------------------------------------------------------------------------------------------
##
## [1] "c2 vs. c3 , number of degs significant at adj.p.val<0.5: 37"
##
## -----------------------------------------------------------------------------------------------------------
## Row.names c2 c3 adj.P.Val V2
## ----------------------------------------------- --------- ------- ----------- -----------------------------
## wgEncodeUwHistoneGm12875H3k04me3StdHotspotsRep1 0.0005212 -0.8239 9.755e-07 GM12875 H3K4me3 Histone Mod
## ChIP-seq Hotspots 1 from
## ENCODE/UW
##
## wgEncodeBroadHistoneGm12878H3k9acStdPk 3.849e-12 0.5541 1.714e-05 GM12878 H3K9ac Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeUwHistoneGm12865H3k04me3StdHotspotsRep2 5.452e-07 -0.8528 2.26e-05 GM12865 H3K4me3 Histone Mod
## ChIP-seq Hotspots 2 from
## ENCODE/UW
##
## wgEncodeBroadHistoneGm12878H3k4me2StdPk 8.782e-09 -0.6556 2.26e-05 GM12878 H3K4me2 Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeUwHistoneGm12865H3k04me3StdHotspotsRep1 2.881e-06 -0.9392 0.0001006 GM12865 H3K4me3 Histone Mod
## ChIP-seq Hotspots 1 from
## ENCODE/UW
##
## wgEncodeUwHistoneGm12864H3k04me3StdHotspotsRep2 0.003202 -0.9901 0.0001157 GM12864 H3K4me3 Histone Mod
## ChIP-seq Hotspots 2 from
## ENCODE/UW
##
## wgEncodeBroadHistoneGm12878H3k79me2StdPk 1.867e-08 -0.8139 0.0001487 GM12878 H3K79me2 Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneDnd41H3k09acPk 0.0001527 0.7596 0.0001965 Dnd41 H3K9ac Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneDnd41H3k04me1Pk 9.105e-08 0.7344 0.0003011 Dnd41 H3K4me1 Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneGm12878H3k04me3StdPkV2 4.708e-08 0.7527 0.0003011 GM12878 H3K4me3 Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
## -----------------------------------------------------------------------------------------------------------
##
## [1] "c2 vs. c4 , number of degs significant at adj.p.val<0.5: 56"
##
## --------------------------------------------------------------------------------------------------------------
## Row.names c2 c4 adj.P.Val V2
## ----------------------------------------------- --------- ---------- ----------- -----------------------------
## wgEncodeUwHistoneGm12875H3k04me3StdHotspotsRep1 0.0005212 -0.3919 3.243e-07 GM12875 H3K4me3 Histone Mod
## ChIP-seq Hotspots 1 from
## ENCODE/UW
##
## wgEncodeBroadHistoneGm12878H3k4me2StdPk 8.782e-09 -0.02811 3.964e-06 GM12878 H3K4me2 Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneGm12878H3k9acStdPk 3.849e-12 -0.1383 3.964e-06 GM12878 H3K9ac Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneGm12878H3k79me2StdPk 1.867e-08 -0.005656 7.731e-06 GM12878 H3K79me2 Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeUwHistoneGm12865H3k04me3StdHotspotsRep2 5.452e-07 -0.2947 1.082e-05 GM12865 H3K4me3 Histone Mod
## ChIP-seq Hotspots 2 from
## ENCODE/UW
##
## wgEncodeBroadHistoneGm12878H3k04me3StdPkV2 4.708e-08 -0.01621 2.189e-05 GM12878 H3K4me3 Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneGm12878H3k9me3StdPk 2.129e-10 -1.413e-05 2.824e-05 GM12878 H3K9me3 Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeUwHistoneGm12864H3k04me3StdHotspotsRep2 0.003202 -0.5261 2.824e-05 GM12864 H3K4me3 Histone Mod
## ChIP-seq Hotspots 2 from
## ENCODE/UW
##
## wgEncodeUwHistoneGm12865H3k04me3StdHotspotsRep1 2.881e-06 -0.3212 2.824e-05 GM12865 H3K4me3 Histone Mod
## ChIP-seq Hotspots 1 from
## ENCODE/UW
##
## wgEncodeBroadHistoneDnd41H3k09acPk 0.0001527 -0.3194 2.824e-05 Dnd41 H3K9ac Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
## --------------------------------------------------------------------------------------------------------------
##
## [1] "c2 vs. c5 , number of degs significant at adj.p.val<0.5: 64"
##
## -----------------------------------------------------------------------------------------------------------
## Row.names c2 c5 adj.P.Val V2
## ----------------------------------------------- --------- ------- ----------- -----------------------------
## wgEncodeUwHistoneGm12875H3k04me3StdHotspotsRep1 0.0005212 0.7538 1.095e-05 GM12875 H3K4me3 Histone Mod
## ChIP-seq Hotspots 1 from
## ENCODE/UW
##
## wgEncodeBroadHistoneGm12878H3k9acStdPk 3.849e-12 0.1729 0.0001041 GM12878 H3K9ac Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeUwHistoneGm12865H3k04me3StdHotspotsRep2 5.452e-07 0.5657 0.0001705 GM12865 H3K4me3 Histone Mod
## ChIP-seq Hotspots 2 from
## ENCODE/UW
##
## wgEncodeBroadHistoneGm12878H3k4me2StdPk 8.782e-09 0.4824 0.0001705 GM12878 H3K4me2 Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneDnd41H3k09acPk 0.0001527 -0.7471 0.0002681 Dnd41 H3K9ac Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneGm12878H3k79me2StdPk 1.867e-08 -0.4384 0.0002681 GM12878 H3K79me2 Histone Mods
## by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeUwHistoneGm12865H3k04me3StdHotspotsRep1 2.881e-06 0.7265 0.0002681 GM12865 H3K4me3 Histone Mod
## ChIP-seq Hotspots 1 from
## ENCODE/UW
##
## wgEncodeUwHistoneGm12864H3k04me3StdHotspotsRep2 0.003202 0.8722 0.0002936 GM12864 H3K4me3 Histone Mod
## ChIP-seq Hotspots 2 from
## ENCODE/UW
##
## wgEncodeBroadHistoneDnd41H3k04me1Pk 9.105e-08 -0.5579 0.0003657 Dnd41 H3K4me1 Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneCd20H3k04me2Pk 6.1e-09 -0.3652 0.0005895 CD20+ H3K4me2 Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
## -----------------------------------------------------------------------------------------------------------
##
## [1] "c3 vs. c5 , number of degs significant at adj.p.val<0.5: 3"
##
## -------------------------------------------------------------------------------------------------------
## Row.names c3 c5 adj.P.Val V2
## ------------------------------------------ ------- ---------- ----------- -----------------------------
## wgEncodeBroadHistoneHsmmH3k27me3StdPk -0.6298 1.409e-09 0.06695 HSMM H3K27me3 Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneDnd41Ezh239875Pk -0.253 0.0006476 0.06695 Dnd41 EZH2 (39875) Histone
## Mods by ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneA549H3k36me3Dex100nmPk 0.08468 -0.0008403 0.08249 A549 DEX 100 nM H3K36me3
## Histone Mods by ChIP-seq
## Peaks from ENCODE/Broad
## -------------------------------------------------------------------------------------------------------
##
## [1] "c4 vs. c5 , number of degs significant at adj.p.val<0.5: 2"
##
## --------------------------------------------------------------------------------------------------
## Row.names c4 c5 adj.P.Val V2
## ------------------------------------- -------- --------- ----------- -----------------------------
## wgEncodeBroadHistoneHsmmH3k27me3StdPk -0.02171 1.409e-09 0.0213 HSMM H3K27me3 Histone Mods by
## ChIP-seq Peaks from
## ENCODE/Broad
##
## wgEncodeBroadHistoneNhekEzh239875Pk -0.1117 0.009518 0.0213 NHEK EZH2 (39875) Histone
## Mods by ChIP-seq Peaks from
## ENCODE/Broad
## --------------------------------------------------------------------------------------------------## [1] "Counts of regulatory elements differentially associated with each group"##
## ---------------------------------
## c1 c2 c3 c4 c5
## -------- ---- ---- ---- ---- ----
## **c1** 0 57 6 34 57
##
## **c2** 0 0 37 56 64
##
## **c3** 0 0 0 0 3
##
## **c4** 0 0 0 0 2
##
## **c5** 0 0 0 0 0
## ---------------------------------Summary
Co-morbidity similarity analysis
We used the data from Hidalgo CA, Blumm N, Barabasi A-L, Christakis NA. PLoS Computational Biology, 5(4):e1000353 doi:10.1371/journal.pcbi.1000353, available at http://barabasilab.neu.edu/projects/hudine/resource/data/data.html. These data provide co-morbidity measurements among pairs of diseases. We map autoimmune disease- and trait names to 3-digits ICD9 codes and evaluate how co-morbidity measurements correlate with regulatory similarity measurements. We used Phi measurement of co-morbidity. The pearson correlation coefficient of Phi and regulatory similarity is:
## [1] 0.3799314Iridescent literature similarity
## [1] "sharedRels correlation with regulatory similarity"
## [1] 0.3395089
## [1] "obsExp correlation with regulatory similarity"
## [1] 0.5154583
## [1] "minMim correlation with regulatory similarity"
## [1] 0.6535677
## [1] "directStr correlation with regulatory similarity"
## [1] 0.1748984
## [1] "relOverlap correlation with regulatory similarity"
## [1] 0.3594159
## [1] "misn correlation with regulatory similarity"
## [1] 0.6776696UMLS literature similarity
## [1] "msh.path correlation with regulatory similarity"
## [1] 0.2743516
## [1] "snomedct.path correlation with regulatory similarity"
## [1] 0.7275952Misc
Distribution of maxMin correlation coefficients
